Abstract

Lymphoid tissue immunopathology is a characteristic feature of chronic HIV/SIV infection in AIDS-susceptible species, but is absent in SIV-infected natural hosts. To investigate factors contributing to this difference, we compared germinal center development and SIV RNA distribution in peripheral lymph nodes during primary SIV infection of the natural host sooty mangabey and the non-natural host pig-tailed macaque. Although SIV-infected cells were detected in the lymph node of both species at two weeks post infection, they were confined to the lymph node paracortex in immune-competent mangabeys but were seen in both the paracortex and the germinal center of SIV-infected macaques. By six weeks post infection, SIV-infected cells were no longer detected in the lymph node of sooty mangabeys. The difference in localization and rate of disappearance of SIV-infected cells between the two species was associated with trapping of cell-free virus on follicular dendritic cells and higher numbers of germinal center CD4+ T lymphocytes in macaques post SIV infection. Our data suggests that fundamental differences in the germinal center microenvironment prevent productive SIV infection within the lymph node germinal centers of natural hosts contributing to sustained immune competency.

Highlights

  • Sooty mangabey (SM) monkeys (Cercocebus atys) are one of many species of Old World African nonhuman primates that serve as natural reservoir hosts of simian immunodeficiency virus (SIV) infection [1,2]

  • During the course of progressive HIV and SIV infection, viral RNA can be localized within two compartments of the germinal center (GC) microenvironment of secondary lymphoid tissues: within productively-infected cells and as cell-free, immune-complexed virions bound to Fc receptors on FDC [20,40,41,42,43]

  • Evidence suggests that infectious virus particles sequestered within immune complexes (IC) as well as virus produced by infected cells within GCs provide a source for new infections of activated CD4+ T lymphocytes and macrophages and facilitate ongoing CD4+ T cell loss, immune activation, and follicular dissolution

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Summary

Introduction

Sooty mangabey (SM) monkeys (Cercocebus atys) are one of many species of Old World African nonhuman primates that serve as natural reservoir hosts of simian immunodeficiency virus (SIV) infection [1,2]. In contrast to Asian macaques, SIV-infected natural hosts maintain normal numbers of CD4+ T lymphocytes and resist the development of immune deficiency and simian AIDS despite lifelong SIV infection, persistent virus replication and elevated plasma viral loads [3,4]. Studies of chronic SIV infection in Indian origin rhesus macaques (RM) have shown that lymphoid tissues undergo similar morphologic changes in architecture throughout the course of SIV infection as seen in chronic HIV infection [5,6]. Normal lymphoid architecture is maintained throughout chronic SIV infection in SM [3,4,8] little is known about lymphoid changes in acute SM SIV infection

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